5ilu: Difference between revisions
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==Autoinhibited ETV4== | |||
<StructureSection load='5ilu' size='340' side='right'caption='[[5ilu]], [[Resolution|resolution]] 1.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5ilu]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ILU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ILU FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.101Å</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5ilu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ilu OCA], [https://pdbe.org/5ilu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ilu RCSB], [https://www.ebi.ac.uk/pdbsum/5ilu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ilu ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/ETV4_HUMAN ETV4_HUMAN] Ewing sarcoma. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ETV4_HUMAN ETV4_HUMAN] Transcriptional activator that binds to the enhancer of the adenovirus E1A gene; the core-binding sequence is 5'[AC]GGA[AT]GT-3'.<ref>PMID:19307308</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Autoinhibition enables spatial and temporal regulation of cellular processes by coupling protein activity to surrounding conditions, often via protein partnerships or signaling pathways. We report the molecular basis of DNA-binding autoinhibition of ETS transcription factors ETV1, ETV4 and ETV5, which are often overexpressed in prostate cancer. Inhibitory elements that cooperate to repress DNA binding were identified in regions N- and C-terminal of the ETS domain. Crystal structures of these three factors revealed an alpha-helix in the C-terminal inhibitory domain that packs against the ETS domain and perturbs the conformation of its DNA-recognition helix. Nuclear magnetic resonance spectroscopy demonstrated that the N-terminal inhibitory domain (NID) is intrinsically disordered, yet utilizes transient intramolecular interactions with the DNA-recognition helix of the ETS domain to mediate autoinhibition. Acetylation of selected lysines within the NID activates DNA binding. This investigation revealed a distinctive mechanism for DNA-binding autoinhibition in the ETV1/4/5 subfamily involving a network of intramolecular interactions not present in other ETS factors. These distinguishing inhibitory elements provide a platform through which cellular triggers, such as protein-protein interactions or post-translational modifications, may specifically regulate the function of these oncogenic proteins. | |||
Structured and disordered regions cooperatively mediate DNA-binding autoinhibition of ETS factors ETV1, ETV4 and ETV5.,Currie SL, Lau DKW, Doane JJ, Whitby FG, Okon M, McIntosh LP, Graves BJ Nucleic Acids Res. 2017 Mar 17;45(5):2223-2241. doi: 10.1093/nar/gkx068. PMID:28161714<ref>PMID:28161714</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5ilu" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Currie SL]] | |||
[[Category: Whitby FG]] | |||